BACKGROUND: Although the importance of quantitative SPECT has increased tremendously due to newly developed therapeutic radiopharmaceuticals, there are still no accreditation programs to harmonize SPECT imaging. Work is currently underway to develop an accreditation for quantitative 177Lu SPECT/CT. The aim of this study is to verify whether the positioning of the spheres within the phantom has an influence on the recovery and thus needs to be considered in SPECT harmonization. In addition, the effects of these recovery coefficients on a potential partial volume correction as well as absorbed-dose estimates are investigated.
METHODS: Using a low-dose CT of a SPECT/CT acquisition, a computerized version of the NEMA body phantom was created using a semi-automatic threshold-based method. Based on the mass-density map, the detector orbit, and the sphere centers, realistic SPECT acquisitions of all possible 720 sphere configurations of both the PET and the SPECT versions of the NEMA Body Phantom were generated using Monte Carlo simulations. SPECT reconstructions with different numbers of updates were performed without (CASToR) and with resolution modeling (STIR). Recovery coefficients were calculated for all permutations, reconstruction methods, and phantoms, and their dependence on the sphere positioning was investigated. Finally, the simulation-based findings were validated using SPECT/CT acquisitions of six different sphere configurations.
RESULTS: Our analysis shows that sphere positioning has a significant impact on the recovery for both of the reconstruction methods and the phantom type. Although resolution modeling resulted in significantly higher recovery, the relative variation in recovery within the 720 permutations was even larger. When examining the extreme values of the recovery, reconstructions without resolution modeling were influenced primarily by the sphere position, while with resolution modeling the volume of the two adjacent spheres had a larger influence. The SPECT measurements confirmed these observations, and the recovery curves showed good overall agreement with the simulated data.
CONCLUSIONS: Our study shows that sphere positioning has a significant impact on the recovery obtained in NEMA sphere phantom measurements and should therefore be considered in a future SPECT accreditation. Furthermore, the single-measurement method normally performed for PVC should be reconsidered to account for the position dependency.

BACKGROUND: CT-based attenuation correction (CT-AC) plays a major role in accurate activity quantification by SPECT/CT imaging. However, the effect of kilovoltage peak (kVp) and quality-reference mAs (QRM) on the attenuation coefficient image (μ-map) and volume CT dose index (CTDIvol) have not yet been systematically evaluated. Therefore, the aim of this study was to fill this gap and investigate the influence of kVp and QRM on CT-AC in 177Lu SPECT/CT imaging.
METHODS: Seventy low-dose CT acquisitions of an Electron Density Phantom (seventeen inserts of nine tissue-equivalent materials) were acquired using various kVp and QRM combinations on a Siemens Symbia Intevo Bold SPECT/CT system. Using manufacturer reconstruction software, 177Lu μ-maps were generated for each CT image, and three low-dose CT related aspects were examined. First, the μ-map-based attenuation values (μmeasured) were compared with theoretical values (μtheoretical). Second, changes in 177Lu activity expected due to changes in the μ-map were calculated using a modified Chang method. Third, the noise in the μ-map was assessed by measuring the coefficient of variation in a volume of interest in the homogeneous section of the Electron Density Phantom. Lastly, two phantoms were designed to simulate attenuation in four tissue-equivalent materials for two different source geometries (1-mL and 10-mL syringes). 177Lu SPECT/CT imaging was performed using three different reconstruction algorithms (xSPECT Quant, Flash3D, STIR), and the SPECT-based activities were compared against the nominal activities in the sources.
RESULTS: The largest relative errors between μmeasured and μtheoretical were observed in the lung inhale insert (range: 18%-36%), while it remained below 6% for all other inserts. The resulting changes in 177Lu activity quantification were -3.5% in the lung inhale insert and less than -2.3% in all other inserts. Coefficient of variation and CTDIvol ranged from 0.3% and 3.6 mGy (130 kVp, 35 mAs) to 0.4% and 0.9 mGy (80 kVp, 20 mAs), respectively. The SPECT-based activity quantification using xSPECT Quant reconstructions outperformed all other reconstruction algorithms.
CONCLUSIONS: This study shows that kVp and QRM values in low-dose CT imaging have a minimum effect on quantitative 177Lu SPECT/CT imaging, while the selection of low values of kVp and QRM reduce the CTDIvol.

UNASSIGNED: The current study aimedto assess condylar activityin patients with unilateral condylar hyperplasia (UCH) with quantitative SPECT/CT.
UNASSIGNED: This retrospective study included patients with UCH who underwent quantitative SPECT/CT. SPECT analysis and quantification of SPECT/CT were performed, and the maximum count per pixel and SUVmax of either side of the condyles were calculated.
UNASSIGNED: 39 patients were included in the analysisand classified into three subgroups according to the percentile differential right-left ratio: inactive group, left active (LA) group, and right active (RA) group. Totally, the SUVmax of the affected side is significantly higher than the unaffected side (active:5.93 ± 2.43 vs inactive:3.62 ± 1.76, P < 0.001), SUVmax-based ratios correlated well with the ratios based on maximum count (R = 0.944, P < 0.001). ROC analysis showed poorSUVmaxperformance in differentiation between theactive condyles and the inactive condyles due to the lower area under the curve (AUC) (0.588). In subgroup analysis, the affected side is significantly higher than the unaffected side in active groups with SUVmax, no significant difference was found between the active sides or the inactive sides of active groups. Interestingly, the SUVmax of the left side was statistically higher than that of the right sidein the inactive group (P = 0.01),while the left side of the right active group has significantlylower activitythan that in the inactive group, meanwhile,the right side showed no significant difference. Furthermore, each side showed no significant difference between the left active group and the inactive group.
UNASSIGNED: SUVmax is not an optimal measurement effectively used to evaluate active condyles. However, SUV ratios correlated well with the count ratios, and the left side of condyles showed a peculiar feature in condyle growth status reflected in radioactivity quantified with SPECT/CT, which needs further study to determine the role in the development of the UCH.

OBJECTIVE: To assess early tumor response with quantitated SPECT/CT and to correlate it with clinical outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with 177Lutetium-PSMA I&T therapy.
METHODS: Single-center, observational study, part of the prospective Swiss national cancer registry study investigating the safety and efficacy of [177Lu]Lu-PSMA I&T (EKNZ: 2021-01271) in mCRPC patients treated with at least two cycles of [177Lu]Lu-PSMA I&T 6-weekly. After the first and second cycle quantitated SPECT/CT (Symbia Intevo, Siemens) was acquired 48 h after injection (three fields of view from head to thigh, 5 s/frame) and reconstructed using xQuant® (48i, 1 s, 10-mm Gauss). Image analysis: The PSMA-positive total tumor volumes (TTV) were semi-automatically delineated using a SUV threshold of 3 with MIMencore® (version 7.1.3, Medical Image Merge Software Inc.). Changes in TTV, highest tumor SUVmax, and total tumor SUVmean between cycles 1 and 2 were calculated and grouped into a) stable or decrease and b) increase. Serum PSA levels were assessed at each therapy cycle and at follow-up until progression or death. Changes in TTV, PSA, SUVmax, and SUVmean were correlated with PSA-progression-free survival (PSA-PFS) and the overall survival (OS) using the Kaplan-Meier methodology (log-rank test).
RESULTS: Between 07/2020 and 04/2022, 111 patients were screened and 73 finally included in the data analysis. The median follow-up was 8.9 months (range 1.4-26.6 months). Stable or decreased TTV at cycle 2 was associated with longer OS (hazard ratio (HR) 0.28, 95% confidence interval (CI) 0.09-0.86, p < 0.01). Similar, stable, or decreased PSA was associated with longer OS (HR 0.21; CI 0.07-0.62, p < 0.01) and PSA-PFS (HR 0.34; 95% CI 0.16-0.72, p < 0.01). Combining TTV and PSA will result in an augmented prognostic value for OS (HR 0.09; CI 0.01-0.63; p < 0.01) and for PSA-PFS (HR 0.11; CI 0.02-0.68; p < 0.01). A reduction of SUVmax or SUVmean was not prognostically relevant, neither for OS (p 0.88 and 0.7) nor for PSA-PFS (p 0.73 and 0.62, respectively).
CONCLUSIONS: Six weeks after initiating [177Lu]Lu-PSMA I&T, TTV and serum PSA appear to be good prognosticators for OS. Combined together, TTV + PSA change demonstrates augmented prognostic value and can better predict PSA-PFS. Larger studies using TTV change prospectively as an early-response biomarker are warranted for implementing management change towards a more personalized clinical practice.

BACKGROUND: Commissioning, calibration, and quality control procedures for nuclear medicine imaging systems are typically performed using hollow containers filled with radionuclide solutions. This leads to multiple sources of uncertainty, many of which can be overcome by using traceable, sealed, long-lived surrogate sources containing a radionuclide of comparable energies and emission probabilities. This study presents the results of a quantitative SPECT/CT imaging comparison exercise performed within the MRTDosimetry consortium to assess the feasibility of using 133Ba as a surrogate for 131I imaging.
METHODS: Two sets of four traceable 133Ba sources were produced at two National Metrology Institutes and encapsulated in 3D-printed cylinders (volume range 1.68-107.4 mL). Corresponding hollow cylinders to be filled with liquid 131I and a mounting baseplate for repeatable positioning within a Jaszczak phantom were also produced. A quantitative SPECT/CT imaging comparison exercise was conducted between seven members of the consortium (eight SPECT/CT systems from two major vendors) based on a standardised protocol. Each site had to perform three measurements with the two sets of 133Ba sources and liquid 131I.
RESULTS: As anticipated, the 131I pseudo-image calibration factors (cps/MBq) were higher than those for 133Ba for all reconstructions and systems. A site-specific cross-calibration reduced the performance differences between both radionuclides with respect to a cross-calibration based on the ratio of emission probabilities from a median of 12-1.5%. The site-specific cross-calibration method also showed agreement between 133Ba and 131I for all cylinder volumes, which highlights the potential use of 133Ba sources to calculate recovery coefficients for partial volume correction.
CONCLUSIONS: This comparison exercise demonstrated that traceable solid 133Ba sources can be used as surrogate for liquid 131I imaging. The use of solid surrogate sources could solve the radiation protection problem inherent in the preparation of phantoms with 131I liquid activity solutions as well as reduce the measurement uncertainties in the activity. This is particularly relevant for stability measurements, which have to be carried out at regular intervals.

Fibroblast activation protein (FAP) is a potential target for tumor diagnosis and treatment because it is selectively expressed on the cell membrane of cancer-associated fibroblasts in most solid tumor stroma. The aim of this study was to develop a 99mTc-labeled fibroblast activation protein inhibitor (FAPI) tracer, evaluate its imaging efficacy in nude mice, and further explore its biodistribution in healthy volunteers and uptake in tumor patients. An FAPI-derived ligand (DP-FAPI) containing d-proline was designed and synthesized as a linker, and a stable hydrophilic 99mTc-labeled complex ([99mTc]Tc-DP-FAPI) was obtained by kit formulation. In vitro cellular uptake and saturation binding assays were performed in FAP-transfected HT-1080 cells (FAP-HT-1080). The biodistribution was characterized, and micro-single-photon emission computed tomography (SPECT) imaging was performed in BALB/c nude mice bearing U87 MG tumors. Furthermore, a first-in-man application was performed in four healthy volunteers and three patients with gastrointestinal tumors. In vitro, the nanomolar Kd values of [99mTc]Tc-DP-FAPI indicated that it had significantly high target affinity for FAP. Biodistribution and micro-SPECT imaging studies showed that [99mTc]Tc-DP-FAPI exhibited high uptake and high tumor-to-nontargeted ratios. The calculated effective dose for [99mTc]Tc-DP-FAPI was approximately <5 mSv in four healthy volunteers. In three patients with gastrointestinal tumors, [99mTc]Tc-DP-FAPI quantitative SPECT/CT revealed high and reliable uptake. [99mTc]Tc-DP-FAPI exhibited high selectivity and affinity for FAP in vitro. The safety and effectiveness of [99mTc]Tc-DP-FAPI in primary tumor imaging have been confirmed by animal and clinical studies, revealing the potential clinical application value of this tracer.

(1) Background: The aim of our study was to assess the feasibility of 99mTcEDDA/HYNIC-TOC SPECT/CT quantitative analysis in evaluating treatment response and disease progression in patients with NETs. (2) Methods: This prospective monocentric study evaluated 35 SPECT/CT examinations performed on 14 patients with neuroendocrine tumours who underwent a baseline and at least one follow-up 99mTcEDDA/HYNIC-TOC scan as part of their clinical management. The examination protocol included a whole-body scan acquired 2 h after the radiotracer’s administration, with the SPECT/CT performed 4 h post-injection. Images were analyzed by two experienced physicians and patients were classified into response categories based on their changes in SUV values. (3) Results: We evaluated 14 baseline studies and 21 follow-up scans, accounting for 123 lesions. A statistically positive correlation has been found between the SUVmax and SUVpeak values in tumoral lesions (p < 0.05). No correlation has been found between the SUV values and the ki67 proliferation index. Finally, 64.29% patients were classified as SD at the end of the study, with only 14.29% of patients exhibiting PD and 21.43% patients with PR. (4) Conclusions: The quantitative analysis of 99mTcEDDA/HYNIC-TOC SPECT/CT data in patients with neuroendocrine tumours could represent an alternative to 68Ga-DOTA-peptides PET/CT for the monitoring and prognosis of NETs.

OBJECTIVE: Quantitative measurements of activity in SPECT are important for radioisotope therapy planning and disease diagnosis. The aim of this manuscript is to develop a robust method to quantify the total activity in a volume-of-interest (VOI) of different quantitative SPECT reconstructions and validate the estimation accuracy.
METHODS: We customized an IEC body phantom using 3D printing technology and made six sphere inserts of 1-6 cm in diameter with at least 3 cm separation. The activity concentration within the spheres was in the range of patient lesion/organ activity. The background activity was then increased from zero to a sphere/background activity concentration of 8:1, 4:1, and 2:1. SPECT data were acquired with Philips Brightview and GE Discovery 670 SPECT/computed tomography (CT) systems under clinical acquisition protocols. Quantitative SPECT images were reconstructed with Hermes SUV-SPECT (both Philips and GE data) and GE Q.Metrix (GE data only). The quantitative SPECT reconstructions are iterative with scatter, CT attenuation correction, and resolution recovery. We quantified the total activity by expanding the sphere VOI to include a spill-out region. Background correction was applied by sampling a region outside the spill-out region. The true fractions (TFs) (total activity/true activity) were measured for all six spheres for all SPECT acquisitions.
RESULTS: The TF is close to 100% for 2-6 cm spheres for zero background, 8:1 and 4:1 sphere/background activity ratios. The TF was found to be unreliable for the 1-cm sphere because of the limit of phantom design. TF accuracy for 2:1 sphere/background ratio was degraded due to significantly large background, inadequate scatter correction and detector count loss.
CONCLUSIONS: The results demonstrated that the proposed quantification method is accurate for objects of different sizes in currently clinical quantitative reconstruction and has the potential for improving the accuracy for therapeutic treatment planning or radiation dosimetry calculations.

We report here a case of sternoclavicular arthritis due to SAPHO syndrome in a 60-year-old female in which quantitative values determined using bone SPECT/CT were useful to evaluate response. After celecoxib and alendronate sodium hydrate therapy, the chief complaints were well relieved and post-treatment Tc-99m HMDP bone SPECT/CT examination showed decreased uptake. The maximum standardized uptake value (SUV), peak SUV, mean SUV, metabolic bone volume, and total bone uptake of the untreated lesion were 18, 16, 10, 17 mL, and 180, respectively, which were decreased to 8, 7, 5, 15 mL, and 75, respectively, after the treatment. In comparison with pre-treatment situation, those parameters were decreased by -56%, -56%, -50%, -12%, and -58%, respectively, following celecoxib and alendronate sodium hydrate therapy, likely reflecting treatment response. Quantitative bone SPECT/CT may be useful to evaluate joint inflammatory activity and treatment response in a patient with osteoartritis.

BACKGROUND: 99mTc-hydrazinonicotinyl-Tyr3-octreotide ([99mTc]-HYNIC-TOC [Tektrotyd]) is a radiopharmaceutical used for the diagnosis of lesions with overexpression of somatostatin receptors. The purpose of this study was to optimize the method and estimate normal ranges for standardized uptake values of Tektrotyd in healthy livers.
METHODS: An analysis of standardized uptake value (SUVs) normal ranges was performed for images acquired in a selected \"healthy group\" of 42 patients evaluated for neuroendocrin tumors. The \"pathological group\" comprised 20 patients with liver lesions detected by scintigraphic imaging. Normal ranges for radiopharmaceutical uptake values were estimated based on the quantitative analysis of images acquired with a GE Healthcare NM/CT 850 gamma camera.
RESULTS: The method for healthy liver segmentation in single photon emission computed tomography/computed tomography (SPECT/CT) was optimized. The normal range of SUVs for the liver was: standardized uptake value body weight (SUVbw) max [5.2-14.0] g/mL and standardized uptake value lean body mass (SUVlbm) [3.5-9.5] g/mL. The relative standard error (relative SE) of activity concentration estimated in the phantom study for the largest hot spheres was: ϕ = 37 mm - 5.9%, ϕ = 28 mm - 7.1%, ϕ = 22 mm - 11.4%, and ϕ = 17 mm - 22%.
CONCLUSIONS: Segmentation in the mid-coronal computed tomography (CT) image, at one-fourth of the height of the liver measured from the top, with a medium-sized volume of interest (VOI) outlined on a given transverse SPECT slice was regarded as the optimal method for estimating normal ranges for standardized uptake values. It is necessary to standardize quantification methods in the SPECT/CT studies. Our work is a step forward in obtaining standardization of SPECT/CT SUV calculation methods. Calculations for radiopharmaceutical uptake in tumors with volumes smaller than 5 mL are biased with a significant measurement error.